It is planned to continue investigations of the pathogenesis of autoimmune thyroid disease. Attempts will be made to learn how immunoregulation is disordered in order to permit a break in tolerance to self antigens. Studies will also be performed to learn by what means immune reactants induced thyroid disease. The hypothesis that the thyroid-stimulating, immunoglobulin (TSI) responsible for the hyperthyroidism of Graves' disease arises as an antiidiotype to anti-TSH will be investigated by seeking anti-TSH activity in serum containing thyroid-stimulating immunoglobulins and TSI in serum containing anti-TSH. In an attempt to learn more about the deranged immunoregulation responsible for autoimmune thyroid diseases, we will produce monoclonal autoantibodies by fusing patients' antibody-forming peripheral blood lymphocytes with myeloma cells to produce autoantibody secreting hybridomas. Monoclonal antibodies derived from such hybridomas will be used as immunogens to raise antiidiotypic sera. In a search for therapeutic approaches to autoantibody synthesis, we will further study antithyroglobulin synthesis in vitro by assessing the response of such synthesis to various drugs and chemicals.